This program is directed toward providing basic and clinical research traiing in fundamentalaspectsof hematology for post-doctoral trainees with M.D. or Ph.D. degrees (currently 59) and basic research training in cell and molecular biology applicable to the broad goals of career training in medical research for pre- doctoral trainees with bachelors degrees who are pursuing Ph.D. and M.D./Ph.D. degrees (currently 40). The areas of research available to trainees reflect the broad range of interests of the training faculty (currently 21) and include: a variety of studies concerning the pathogenesis of thrombotic disorders; explorationof methods for gene therapy of coagulation and lysosomal enzyme defects; the pathways of phosphoinositide metabolism; hematopoesis and bone marrow failure, molecular basis for protein trafficking in mammalian cells; regulation of hemoglobin switching; role of platelets and angiogenesis in metastasisand molecular dissection of the interactions of human retroviruses. All trainees will conduct original investigations and participate in our seminar program. Predoctoral trainees will follow the curriculum of the graduate Division of Biology and Biomedical Sciences at Washington University. The major facilities of the research training program are comprised of 40,000 square feet of laboratoryspace in the Clinical Sciences Research Building and 20,000 square feet in the Southwest Tower which house the Divisions of Hematology and Molecular Oncology and our Howard Hughes Research unit. These facilities include all major items of equipment for modern biochemical, molecular biological and immunological research, including tissue-culture facilities for stem cell culture. We also have mouse facilities for embryo injection and transfer for the construction of transgenic and gene knockout mice. We are requesting continuing support for 8 postdoctoral trainees per year who will be trained from two to three years (i.e., 3 first year trainees; 3 second year trainees and 2 third year trainees),' and support for 7 predoctoral trainees who will be trained from three to four years.